Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Measurement of Socioeconomic Factors
2.3. Ascertainment of Genetic Risk
2.4. Two-Sample Mendelian Randomization Study
2.5. Statistical Analysis
3. Results
3.1. Participant Characteristics
3.2. Association between TERT SNPs and TCa Risk
3.3. Genetic Susceptibility, Socioeconomic Factors, and TCa Risk
3.4. Interaction between Genetic and Socioeconomic Factors on TCa Risk
3.5. Examination of Causal Effect by MR Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cases | Controls | p-Value | |
---|---|---|---|
N | 1026 | 501,368 | |
Age, years (mean ± SD) | 56.9 ± 7.7 | 56.5 ± 8.1 | 0.170 |
Sex | <0.001 | ||
Female | 781 (76.1) | 272,534 (54.4) | |
Male | 245 (23.9) | 228,834 (45.6) | |
Annual household income | 0.001 | ||
≤£30,999 | 419 (41.2) | 204,912 (41.4) | |
£31,000–£51,999 | 242 (23.8) | 110,508 (22.3) | |
≥£52,000 | 180 (17.7) | 108,991 (22.0) | |
Not known/Refuse to answer | 175 (17.3) | 70,953 (14.3) | |
Missing | 10 | 6004 | |
Age finishing full-time education | 0.740 | ||
≤15 years | 206 (30.7) | 103,019 (30.6) | |
16–20 years | 392 (58.4) | 200,877 (59.7) | |
≥21 years | 60 (8.9) | 26,320 (7.8) | |
Not known/Refuse to answer | 13 (1.9) | 6451 (1.9) | |
Missing | 355 | 164,701 | |
Education level | 0.260 | ||
College/university or above | 352 (34.6) | 160,765 (32.4) | |
High school | 121 (11.9) | 55,186 (11.1) | |
Middle school or below | 363 (35.7) | 190,216 (38.3) | |
Not known/Refuse to answer | 181 (17.8) | 90,568 (18.2) | |
Missing | 9 | 4633 | |
Employment status | 0.004 | ||
Employed | 537 (52.4) | 286,529 (57.2) | |
Unemployed | 472 (46.1) | 209,105 (41.8) | |
Not known/Refuse to answer | 15 (1.5) | 4864 (1.0) | |
Missing | 2 | 870 | |
Job involves heavy work | 0.026 | ||
Never/rarely | 384 (71.0) | 186,824 (64.9) | |
Sometimes | 97 (17.9) | 61,951 (21.5) | |
Usually/always | 60 (11.1) | 38,808 (13.5) | |
Not known/Refuse to answer | 0 (0.0) | 335 (0.1) | |
Missing | 485 | 213,450 | |
Job involves walking or standing | 0.670 | ||
Never/rarely | 198 (36.6) | 101,236 (35.2) | |
Sometimes | 168 (31.1) | 88,036 (30.6) | |
Usually/always | 175 (32.3) | 98,265 (34.1) | |
Not known/Refuse to answer | 0 (0.0) | 379 (0.1) | |
Missing | 485 | 213,452 | |
Job involves night shift work | 0.280 | ||
Never/rarely | 58 (53.2) | 25,583 (49.5) | |
Sometimes | 23 (21.1) | 14,583 (28.2) | |
Usually/always | 28 (25.7) | 11,191 (21.6) | |
Not known/Refuse to answer | 0 (0.0) | 343 (0.7) | |
Missing | 917 | 449,668 | |
Household size | 0.260 | ||
One | 186 (18.2) | 92,701 (18.6) | |
Two | 506 (49.5) | 232,201 (46.5) | |
Three or more | 326 (31.9) | 171,925 (34.4) | |
Not known/Refuse to answer | 5 (0.5) | 2283 (0.5) | |
Missing | 3 | 2258 | |
Frequency of friend/family visits | 0.057 | ||
<1 time/week | 194 (19.1) | 108,137 (21.8) | |
1 time/week | 348 (34.2) | 176,024 (35.4) | |
≥2 times/week | 467 (45.9) | 209,292 (42.1) | |
Not known/Refuse to answer | 8 (0.8) | 3270 (0.7) | |
Missing | 9 | 4645 | |
Frequency of confiding in others | 0.082 | ||
<1 time/month | 182 (17.8) | 98,879 (19.8) | |
1 time/month to 4 times/week | 283 (27.6) | 125,673 (25.1) | |
≥5 times/week | 531 (51.9) | 257,973 (51.5) | |
Not known/Refuse to answer | 28 (2.7) | 17,931 (3.6) | |
Missing | 2 | 912 |
SNP ID | Position * | Location | Alleles # | RAF | OR (95% CI) | p-Value |
---|---|---|---|---|---|---|
rs145685051 | 1276736 | Intron 6 | G/A | 0.017 | 1.41 (1.05–1.90) | 0.024 |
rs10054203 | 1279964 | Intron 4 | C/G | 0.399 | 1.14 (1.03–1.25) | 0.008 |
rs2242652 | 1280028 | Intron 4 | A/G | 0.189 | 1.12 (1.00–1.25) | 0.049 |
rs13167280 | 1280477 | Intron 3 | A/G | 0.119 | 1.18 (1.03–1.34) | 0.018 |
rs7726159 | 1282319 | Intron 3 | A/C | 0.327 | 1.19 (1.09–1.31) | 2.23 × 10−4 |
rs7725218 | 1282414 | Intron 3 | A/G | 0.341 | 1.18 (1.07–1.29) | 6.17 × 10−4 |
rs72709458 | 1283755 | Intron 2 | T/C | 0.201 | 1.14 (1.02–1.27) | 0.024 |
rs4449583 | 1284135 | Intron 2 | T/C | 0.325 | 1.20 (1.10–1.32) | 1.05 × 10−4 |
rs62332583 | 1286037 | Intron 2 | T/C | 0.014 | 1.48 (1.07–2.03) | 0.016 |
rs2736100 | 1286516 | Intron 2 | C/A | 0.503 | 1.11 (1.01–1.21) | 0.026 |
rs74682426 | 1289975 | Intron 2 | A/C | 0.133 | 1.15 (1.01–1.31) | 0.031 |
rs2735940 | 1296486 | Promoter | A/G | 0.514 | 1.10 (1.00–1.20) | 0.045 |
Crude Model | Adjusted Model | |||
---|---|---|---|---|
OR (95%CI) | p-Value | OR (95%CI) | p-Value | |
PRS levels | ||||
Low | 1.00 | 1.00 | ||
Medium | 1.63 (1.36–1.94) | <0.001 | 1.63 (1.36–1.95) | <0.001 |
High | 2.47 (2.09–2.91) | <0.001 | 2.49 (2.10–2.94) | <0.001 |
Annual household income | ||||
≥£52,000 | 1.00 | 1.00 | ||
<£52,000 | 1.27 (1.08–1.50) | 0.005 | 1.23 (1.02–1.47) | 0.029 |
Age finishing full-time education | ||||
20 years or less | 1.00 | 1.00 | ||
21 years or more | 1.01 (0.85–1.19) | 0.952 | 1.02 (0.85–1.21) | 0.852 |
Education level | ||||
High school or below | 1.00 | 1.00 | ||
College/university or above | 1.15 (1.00–1.32) | 0.049 | 1.19 (1.02–1.39) | 0.023 |
Employment status | ||||
Employed | 1.00 | 1.00 | ||
Unemployed | 1.20 (1.06–1.36) | 0.003 | 1.10 (0.92–1.32) | 0.315 |
Household size | ||||
Three or more | 1.00 | 1.00 | ||
Two or less | 1.12 (0.98–1.28) | 0.084 | 1.04 (0.90–1.21) | 0.586 |
Frequency of friend/family visits | ||||
<1 time/week | 1.00 | 1.00 | ||
≥1 time/week | 1.18 (1.01–1.37) | 0.039 | 1.04 (0.899–1.22) | 0.608 |
Frequency of confiding in others | ||||
<1 time/week | 1.00 | 1.00 | ||
≥1 time/week | 1.15 (0.98–1.35) | 0.083 | 1.04 (0.88–1.22) | 0.650 |
PRS Levels | Sample Size | Socioeconomic Factors | OR (95%CI) | p-interaction |
---|---|---|---|---|
Annual household income | ||||
Low | 35,664 | ≥£52,000 | 1.00 | 0.049 |
102,771 | <£52,000 | 1.56 (1.00–2.46) | ||
Medium | 35,487 | ≥£52,000 | 1.00 | |
102,900 | <£52,000 | 1.46 (1.03–2.08) | ||
High | 35,820 | ≥£52,000 | 1.00 | |
103,109 | <£52,000 | 1.03 (0.80–1.32) | ||
Education level | ||||
Low | 62,487 | High school or below | 1.00 | 0.179 |
70,275 | College/university or above | 1.16 (0.81–1.65) | ||
Medium | 61,932 | High school or below | 1.00 | |
70,740 | College/university or above | 1.02 (0.77–1.34) | ||
High | 61,810 | High school or below | 1.00 | |
70,510 | College/university or above | 1.32 (1.06–1.65) | ||
Employment status | ||||
Low | 93,148 | Employed | 1.00 | 0.137 |
67,481 | Unemployed | 1.11 (0.73–1.69) | ||
Medium | 92,695 | Employed | 1.00 | |
67,966 | Unemployed | 1.15 (0.83–1.59) | ||
High | 92,849 | Employed | 1.00 | |
67,855 | Unemployed | 1.05 (0.80–1.36) | ||
Frequency of friend/family visits | ||||
Low | 35,528 | <1 time/week | 1.00 | 0.001 |
125,397 | ≥1 time/week | 0.70 (0.47–1.04) | ||
Medium | 35,261 | <1 time/week | 1.00 | |
125,749 | ≥1 time/week | 0.94 (0.68–1.31) | ||
High | 34,894 | <1 time/week | 1.00 | |
126,256 | ≥1 time/week | 1.36 (1.02–1.81) |
Genotyping of rs4449583 | Sample Size | Socioeconomic Factors | OR (95%CI) | p-interaction |
---|---|---|---|---|
Annual household income | ||||
CC | 46,161 | ≥£52,000 | 1.00 | 0.006 |
134,601 | <£52,000 | 1.45 (1.06–1.99) | ||
CT | 45,346 | ≥£52,000 | 1.00 | |
129,076 | <£52,000 | 1.12 (0.85–1.47) | ||
TT | 11,000 | ≥£52,000 | 1.00 | |
30,979 | <£52,000 | 1.03 (0.63–1.68) | ||
Education level | ||||
CC | 81,281 | High school or below | 1.00 | 0.670 |
91,088 | College/university or above | 1.24 (0.97–1.59) | ||
CT | 77,849 | High school or below | 1.00 | |
88,780 | College/university or above | 1.08 (0.86–1.37) | ||
TT | 18,833 | High school or below | 1.00 | |
21,482 | College/university or above | 1.30 (0.84–2.00) | ||
Employment status | ||||
CC | 120,841 | Employed | 1.00 | 0.179 |
88,336 | Unemployed | 1.31 (0.97–1.75) | ||
CT | 116,324 | Employed | 1.00 | |
85,626 | Unemployed | 1.02 (0.77–1.36) | ||
TT | 28,228 | Employed | 1.00 | |
20,447 | Unemployed | 0.94 (0.57–1.57) | ||
Frequency of friend/family visits | ||||
CC | 45,322 | <1 time/week | 1.00 | 0.720 |
164,281 | ≥1 time/week | 1.11 (0.81–1.51) | ||
CT | 43,871 | <1 time/week | 1.00 | |
158,583 | ≥1 time/week | 1.09 (0.82–1.46) | ||
TT | 10,565 | <1 time/week | 1.00 | |
38,210 | ≥1 time/week | 1.02 (0.61–1.71) |
Phenotype | Instrument | Effect Size | Heterogeneity | Pleiotropy | ||||||
---|---|---|---|---|---|---|---|---|---|---|
SNPs (n) | F-Stat | R2 (%) | OR (95%CI) | p | Q-Stat | p | I2 (%) | MR-Egger Intercept | p | |
Lower income | 47 | 57.12 | 0.70 | 1.20 (0.61–2.36) | 0.589 | 59.42 | 0.089 | 22.58 | 0.00 | 0.945 |
College/university degree | 241 | 9.05 | 0.68 | 0.93 (0.50–1.71) | 0.811 | 262.77 | 0.150 | 8.66 | 0.02 | 0.051 |
Unemployed | 9 | 10.48 | 0.02 | 235.78 (0.29–19,204) | 0.110 | 7.81 | 0.452 | 0.00 | −0.03 | 0.327 |
Frequent friend/family visits | 21 | 47.70 | 0.25 | 1.10 (0.32–3.72) | 0.881 | 28.72 | 0.093 | 30.37 | 0.05 | 0.413 |
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Share and Cite
Li, Y.; Zhan, Y.; Mao, W.; Wang, B.; Dong, P.; Na, R. Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants. Cancers 2023, 15, 5028. https://doi.org/10.3390/cancers15205028
Li Y, Zhan Y, Mao W, Wang B, Dong P, Na R. Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants. Cancers. 2023; 15(20):5028. https://doi.org/10.3390/cancers15205028
Chicago/Turabian StyleLi, Yu, Yongle Zhan, Wei Mao, Baoxin Wang, Pin Dong, and Rong Na. 2023. "Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants" Cancers 15, no. 20: 5028. https://doi.org/10.3390/cancers15205028